DNP 810 Week 3 Case Study Part 2: Huntington’s Disease
Case Study Part 2: Huntington’s Disease
Huntington’s disease (HD) is a hereditary condition transmitted as an autosomal dominant trait during conception. It is a movement disorder that causes neurologic and behavioral symptoms that typically become evident from 30 to 50 years and aggravate in the next one to two decades of a person’s life (McColgan & Tabrizi, 2018). It is approximated that 30,000 individuals in the United States (US) have HD, and another 20,000 to 50,000 are assumed to carry the gene. Males and females are equally affected at a time in their lives when they are highly productive. HD usually causes chorea, neuropsychiatric symptoms, and dementia during middle age, and most patients ultimately require institutionalization (McColgan & Tabrizi, 2018). The purpose of this paper is to discuss the chromosomal analysis in HD, causes, and gene mutation.
Indications for Chromosomal Analysis
The direct test for the HD gene involves cysteine-adenosine-guanine (CAG) analysis and repeat length. The chromosomal analysis enables healthcare providers to offer genetic counseling and psychological support services that facilitate predictive testing in a timely, sensitive, and informed fashion (Goldman et al., 2021). Indications for chromosomal analysis in HD include predictive testing in an asymptomatic person at risk for carrying the HD gene to confirm a suspected HD diagnosis and for prenatal diagnosis and preimplantation genetic diagnosis (PGD). The common reasons for predictive testing include making plans on marriage, reproduction, finances, and the need to alleviate uncertainty (Goldman et al., 2021). However, the choice to undergo a predictive test chromosomal analysis for HD must always be informed, deliberated, and freely chosen.
Confirmatory testing by chromosomal analysis of the HD gene is indicated at or following a clinical diagnosis of HD. A CAG replicate expansion in a patient with HD symptoms validates the clinical impression and supports HD diagnosis. In prenatal diagnosis, Chorionic Villus Sampling (CVS) and amniocentesis indicate if the parent is at risk or is positive for the HD gene (Garrett et al., 2019). CVS is performed from 10-12th week gestation, while amniocentesis is done from 14th to 20th week. Furthermore, the PGD test is conducted on a single cell obtained through a needle biopsy from the eight-cell embryo. The chromosomal analysis is carried out on the DNA from the single-cell, facilitating the detection of the HD replicates sizes for the specific embryo. It is worth noting that children should not undergo chromosomal analysis for HD except if there is a medically convincing reason, like a clinical diagnosis or a strong clinical suspicion of HD (Garrett et al., 2019). In these circumstances, the chromosomal analysis should come after a thorough neurological and neuropsychological examination.
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Causes of Huntington’s Disease
HD is attributed to selective dysfunction of the neurons and ensuing neuronal in the cerebral cortex, striatum, and other brain regions. It is attributed to the elongation of CAG replicates on the short arm of chromosome 4p16.3 in the Huntingtin (HTT) gene. The mutation results in an unusually long expansion of the polyglutamine in the HTT protein, resulting in neurodegeneration (Ghosh & Tabrizi, 2018). The HTT protein’s gene encodes are involved in synaptic function and have a major role in the post-embryonic period. Besides, it is supposed to have anti-apoptotic functions and protects against the toxic mutant HTT. Some evidence shows that the mutant protein causes an addition and a loss of function.
Origin of Huntington’s Disease and Considerations for Practice and Patient Education
The HD gene is evident from conception and is inherited in an autosomal dominant manner. This means that every offspring of an affected parent, regardless of sex, has a 50% probability of inheriting the HD gene. HD is a single gene disorder attributed to a mutation in the HD gene (IT15) on chromosome 4 (Ghosh & Tabrizi, 2018). This causes unusual replication of the DNA sequence CAG, which normally codes for the amino acid glutamine. It results in a large protein referred to as huntingtin, which has an extended stretch of polyglutamine residues that build up within neurons contributing to HD through unknown mechanisms. The more CAG replicates, the earlier the onset of HD and the more acute its expression (Ghosh & Tabrizi, 2018). The number of CAG replications increases with consecutive generations when the father transmits the mutation and can cause increasingly adverse phenotypes within a family over time.
In clinical practice, the clinician should consider that there is no existing treatment for HD, and the only approach to prevent gene transmission is for affected individuals to avoid having biological children. Patient education should involve genetic counseling, which is crucial for the offspring of patients with HD. The DNP-nurse should educate patients at risk for HD to be tested to establish whether they have an HD gene mutation. However, before the test, the DNP-nurse should counsel patients to ensure that they have voluntarily decided to undergo testing (McColgan & Tabrizi, 2018). Besides, counseling helps identify whether the advantages of knowing the results outweigh the risks of a positive result like mental distress.
Gene Mutation of Huntington’s Disease
The HD gene mutation is considered a multiple repeats of the particular base triplet CAG, which increases the gene’s length. HD is passed on as a dominant Mendelian gene. An autosomal dominant trait with a high penetrance means that an individual who inherits just one mutated allele has almost a 100% probability of developing HD (Gatto et al., 2020). Individuals who inherit the HD gene mutation from their father have an early onset of the disease and a shorter life expectancy compared to those who inherit it from their mother. Furthermore, there are differences in HD based on the size or length of the HD gene mutation. The longer the mutation, the more critical the HD is at an earlier age. Patients commonly have the HTT allele with CAG repeats ranging from 36 to 55. Besides, persons with juvenile-onset the disorder typically have CAG repeats above 60 (Gatto et al., 2020). However, individuals with alleles ranging from 27 to 35 do not exhibit signs of HD but are inclined to repeat instability.
HD is a neurodegenerative disorder caused by a dominantly inherited CAG replicate expansion in the huntingtin gene on chromosome 4. Chromosomal analysis for HD includes predictive testing in at-risk patients, confirmation of a suspected HD diagnosis, prenatal diagnosis, and preimplantation genetic diagnosis. The HD gene mutation has various expressions based on if an individual inherits it from the father or mother. Genetic counseling is crucial before genetic testing, and the DNP-nurse should ensure that the patient’s decision is voluntary.
Garrett, J. R., Lantos, J. D., Biesecker, L. G., Childerhose, J. E., Chung, W. K., Holm, I. A., … & Brothers, K. (2019). Rethinking the “open future” argument against predictive genetic testing of children. Genetics in Medicine, 21(10), 2190-2198. https://doi.org/10.1038/s41436-019-0483-4
Gatto, E. M., Rojas, N. G., Persi, G., Etcheverry, J. L., Cesarini, M. E., & Perandones, C. (2020). Huntington’s disease: Advances in the understanding of its mechanisms. Clinical parkinsonism & related disorders, 3, 100056. https://doi.org/10.1016/j.prdoa.2020.100056
Ghosh, R., & Tabrizi, S. J. (2018). Huntington disease. Handbook of Clinical Neurology, 255–278. https://doi.org/10.1016/b978-0-444-63233-3.00017-8
Goldman, J., Xie, S., Green, D., Naini, A., Mansukhani, M. M., & Marder, K. (2021). Predictive testing for neurodegenerative diseases in the age of next‐generation sequencing. Journal of Genetic Counseling, 30(2), 553-562. https://doi.org/10.1002/jgc4.1342
McColgan, P., & Tabrizi, S. J. (2018). Huntington’s disease: a clinical review. European journal of neurology, 25(1), 24–34. https://doi.org/10.1111/ene.13413
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